DESCRIPTION 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) is the most toxic of the dioxins and is one of the most potent environmental toxins ever investigated by the EPA. Our laboratory has recently shown a dose-dependent inhibition of ovulation by TCDD. Although the exact mechanisms of this ovulation blockade is unknown, the effect seems primarily to be the result of direct action(s) on the ovary and is exaggerated by previous exposure to estrogens (another class of environmental endocrine disrupter). Such interruption of ovulation might well be one mechanism by which environmental estrogens and TCDD diminish fertility. Our current work is intended to learn how TCDD and estrogens interact in the blockade of ovulation Using a hypophysectomized rt model, the experiments outlined in this proposal are intended to 1) characterize the ability of estrogens to exaggerate the suppression of ovulation by TCDD 2) determine the target tissues of estrogen and TCDD within the ovary 3) assess the interaction of estrogen and TCDD with the aryl hydrocarbon receptor gene. The long term goal of this project is to determine the mechanism by which TCDD and estrogens interact to prevent ovulation and apply this knowledge to the study of environmental estrogens and dioxins.